A study of the mechanisms by which histamine stimulates cardiac muscle and the modification of this activity by environmental factors and drugs: (1) modification of histamine initiated mechanical activity by alterations in the extracellular milieu (pH, temperature, ions, relative hypoxia etc.); (2) studies of some of the biochemically mediated changes which occur as a result of receptor stimulation and modification of receptor activity by pharmacologically active H1- and H2-agonists and antagonists; (3) measurements of tissue histamine content and its alteration by various conditions and compounds; and (4) an attempt to isolate and characterize the histamine receptor(s) (H1- and H2-) using several biochemical techniques.